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      Season and region of birth as risk factors for coeliac disease a key to the aetiology?

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          Coeliac disease (CD) incidence has increased in recent decades, characterised by variations according to sex, age at diagnosis, year of birth, month of birth and region of birth. Genetic susceptibility and exposure to gluten are the necessary factors in CD aetiology, although several environmental factors are considered.


          A nationwide prospective cohort longitudinal study was conducted consisting of 1 912 204 children aged 0–14.9 years born in Sweden from 1991 to 2009. A total of 6569 children were diagnosed with biopsy-verified CD from 47 paediatric departments. Using Cox regression, we examined the association between CD diagnosis and season of birth, region of birth and year of birth.


          Overall, CD risk was higher for children born during spring, summer and autumn as compared with children born during winter: adjusted HR for spring 1.08 (95% CI 1.01 to 1.16), summer 1.10 (95% CI 1.03 to 1.18) and autumn 1.10 (95% CI 1.02 to 1.18). Increased CD risk was highest if born in the south, followed by central Sweden when compared with children born in northern Sweden. Children diagnosed at <2 years had an increased CD risk if born in spring while those diagnosed at 2–14.9 years the risk was increased for summer and autumn births. The birth cohort of 1991–1996 had increased CD risk if born during spring, for the 1997–2002 birth cohort the risk increased for summer and autumn births, while for the birth cohort of 2003–2009 the risk was increased if born during autumn.


          Season of birth and region of birth are independently and jointly associated with increased risk of developing CD during the first 15 years of life. Seasonal variation in infectious load is the likely explanation.

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          Most cited references 32

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          Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition.

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            Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study.

            Few studies have assessed the role of specific gastrointestinal infections in celiac disease. We investigated whether increased frequency of rotavirus infection, a common cause of gastrointestinal infection and inflammation, predicts increased risk of celiac disease autoimmunity. A cohort of 1,931 children from the Denver metropolitan area who carried celiac disease human leukocyte antigen (HLA) risk alleles were followed from infancy for development of celiac disease autoimmunity, defined as positivity at two or more subsequent clinic visits for tissue transglutaminase (tTG) autoantibodies measured using a radioimmunoassay with human recombinant tTG. Blood samples were obtained at ages 9, 15, and 24 months, and annually thereafter. Rotavirus antibodies were assayed using an indirect enzyme immunoassay in serial serum samples from each case and two matched controls. Frequency of infections were estimated by the number of increases (> 2 assay coefficient of variation) in rotavirus antibody between clinic visits. Fifty-four cases developed celiac disease autoimmunity at a median age of 4.4 yr. Thirty-six had an intestinal biopsy, of which 27 (75%) were positive for celiac disease. Frequent rotavirus infections predicted a higher risk of celiac disease autoimmunity (compared with zero infections, rate ratio 1.94, 95% confidence interval [CI] 0.39-9.56, for one infection and rate ratio 3.76, 95% CI 0.76-18.7, for > or = 2 infections, rate ratio for trend per increase in number of infections = 1.94, 95% CI 1.04-3.61, p = 0.037). The result was similar after adjustment for gender, ethnic group, maternal education, breast-feeding, day-care attendance, number of siblings, season of birth, and number of HLA DR3-DQ2 haplotypes. This prospective study provides the first indication that a high frequency of rotavirus infections may increase the risk of celiac disease autoimmunity in childhood in genetically predisposed individuals.
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              Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic.

              Sweden experienced a marked epidemic of celiac disease between 1984 and 1996 in children younger than 2 years of age, partly explained by changes in infant feeding. The objective of this study was to determine the prevalence of celiac disease in 12-year-olds born during the epidemic (1993), including both symptomatic and screening detected cases. All sixth-grade children in participating schools were invited (n = 10,041). Symptomatic and, therefore, previously diagnosed celiac disease cases were ascertained through the National Swedish Childhood Celiac Disease Register and/or medical records. All serum samples were analyzed for antihuman tissue transglutaminase (tTG)-IgA (Celikey), and serum-IgA, and some for tTG-IgG and endomysial antibodies. A small intestinal biopsy was recommended for all children with suspected undiagnosed celiac disease. Participation was accepted by 7567 families (75%). Previously diagnosed celiac disease was found in 67 children; 8.9/1000 (95% confidence interval [CI] 6.7-11). In another 192 children, a small intestinal biopsy was recommended and was performed in 180. Celiac disease was verified in 145 children, 20/1000 (95% CI 17-23). The total prevalence was 29/1000 (95% CI 25-33). The celiac disease prevalence of 29/1000 (3%)-with two thirds of cases undiagnosed before screening-is 3-fold higher than the usually suggested prevalence of 1%. When these 12-year-olds were infants, the prevailing feeding practice was to introduce gluten abruptly, often without ongoing breast-feeding, which might have contributed to this unexpectedly high prevalence.

                Author and article information

                Arch Dis Child
                Arch. Dis. Child
                Archives of Disease in Childhood
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                December 2016
                15 August 2016
                : 101
                : 12
                : 1114-1118
                [1 ]Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University , Umeå, Sweden
                [2 ]Department of Food and Nutrition, Umeå University , Umeå, Sweden
                [3 ]Department of Clinical Sciences, Pediatrics, Umeå University , Umeå, Sweden
                Author notes
                [Correspondence to ] Fredinah Namatovu, Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå SE-901 87, Sweden; fredinah.namatovu@
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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                general paediatrics, gastroenterology, epidemiology


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